Photodynamic therapy (PDT) exploits the selective uptake of a photosensitizer in tumors and other hyperproliferative target tissues. Since the difference between target tissue uptake of photosensitizer and that of normal tissue is at best only marginal, uniform delivery of light is crucial to attain optimal photodynamic effect. Some degree of selectively may be achieved by simply aiming the light beam at the desired target tissue, but to truly offer selectively of action on target tissue versus adjacent or intermixed normal tissue, selective uptake of dye into target tissue and uniform delivery of light is required. Variations in applied light intensity may result in certain areas within a treatment field receiving over or under dosing. Thus, tumor tissue may be inadvertently spared destruction if present in an area of under treatment, while normal tissue may be destroyed if light intensity is focally increased in a certain area.
Clinical applications of PDT have used free optical fibers as well as diffusing lenses to administer laser light to treatment areas. Light delivery is usually accomplished with an argon-pumped dye laser using a single wavelength of light. This allows for easy calculation of delivered light dose and an estimate of photodynamic effect.
The selective uptake of dihematoporphyrum ether (DHE) and other photosensitizers within tumors, or other rapidly proliferating tissues, is the basis for most of the therapeutic benefit of PDT. Although photodynamic effect may be directed to specific areas by selective placement of the treatment beam, this affords little benefit in treating most diseases over other descriptive modalities. Selective destruction of target tissue over adjacent, or even intermixed, normal tissue depends upon selective uptake of photosensitizer in target tissue as compared to normal tissue. This has been shown to occur with numerous tumors and other proliferative disorders in vivo, with a variety of photosensitizers. Relative differences in the uptake of DHE into target tissue versus skin, have been shown to be 1.08, 1.8, 2.2, 3.9 and 4.2 in various animal models. Although newer photosensitizers such as the phthalocyanines and 5-ALA-induced protoporphyrin IX may result in even higher relative differences in photosensitizer uptake in target tissue, normal tissues still retain significant amount of photosensitizer in most cases.
Tissue DHE content is a function of the administered DHE and its degree of retention within various tissues. Because differences between target tissue DHE content and normal structures is relative and not absolute, uniform light delivery is imperative to ensure destruction of tumors while sparing normal healthy tissue.